4mbc
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4mbc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_GA47373 Streptococcus pneumoniae GA47373]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MBC FirstGlance]. <br> | <table><tr><td colspan='2'>[[4mbc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_GA47373 Streptococcus pneumoniae GA47373]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MBC FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=28G:1-{5-[2-(MORPHOLIN-4-YL)ETHOXY]-6-(PYRIDIN-3-YL)[1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL}-3-PROP-2-EN-1-YLUREA'>28G</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=28G:1-{5-[2-(MORPHOLIN-4-YL)ETHOXY]-6-(PYRIDIN-3-YL)[1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL}-3-PROP-2-EN-1-YLUREA'>28G</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mbc OCA], [https://pdbe.org/4mbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mbc RCSB], [https://www.ebi.ac.uk/pdbsum/4mbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mbc ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mbc OCA], [https://pdbe.org/4mbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mbc RCSB], [https://www.ebi.ac.uk/pdbsum/4mbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mbc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration of side-chains at the thiazolopyridine ring C-5 position to access the ribose/solvent pocket. Potent compounds with GyrB IC50 </=1 nM and Mtb MIC </=0.1 microM were obtained with certain combinations of side-chains at C-5 position and heterocycles at C-6 position of the thiazolopyridine core. Substitutions at C-5 also enabled optimization of physicochemical properties. Representative compounds were co-crystallized with Streptococcus pneumoniae (Spn) ParE; these confirmed the binding modes predicted by the homology model. The target link to GyrB was confirmed by genetic mapping of mutations conferring resistance to thiazolopyridine ureas. The compounds are bactericidal in vitro and efficacious in vivo in an acute murine model of tuberculosis. | ||
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| - | Thiazolopyridine Ureas as Novel Antitubercular Agents Acting Through Inhibition of DNA Gyrase B.,Ghorpade SR, Kale M, Raichurkar A, Hameed P S, Waterson D, McKinney D, Mramaiah M, Koushik K, Jena LK, Shinde V, Rudrapatna S, Humnabadkar V, Madhavapeddi P, Basavarajappa H, Ghosh A, Murthy R, Guptha S, Sharma S, Vachaspati P, K N MK, Giridhar J, Reddy J, Panduga V, Ganguly S, Ahuja V, Gaonkar S, C N NK, Ogg D, Tucker JA, Boriack-Sjodin PA, de Sousa SM, Sambandamurthy V, Kranthi U, Barde S J Med Chem. 2013 Oct 3. PMID:24088190<ref>PMID:24088190</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4mbc" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]] | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of Streptococcus pneumonia ParE in complex with AZ13053807
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